Microvascular oxygen consumption was greater in sickle cell patients than in healthy individuals (median interquartile range; sickle cell: 0.91 0.75-1.07 vs healthy: 0.75 0.62-0.94 -&#916;HbO2/min, P < .05) and was elevated further during acute pain crisis (crisis: 1.10 0.78-1.30 vs recovered: 0.88 0.76-1.03 -&#916;HbO2/min, P < .05). Increased microvascular oxygen consumption during pain crisis could affect the local oxygen saturation of hemoglobin when oxygen delivery is limiting. Identifying the mechanisms of elevated oxygen consumption during pain crisis might lead to the development of new therapeutic interventions.